Systems for analyzing bodily fluid samples generally are classified as either “wet reagent analytical systems” or “dry reagent analytical systems.”
Dry reagent analytical systems typically comprise test elements with integrated reagents. Such test elements are typically test strips, in which a fluid sample dissolves the reagents in the test strip and the reaction thereof results in a measurable change of a measured value. The measured value is measured on the test element using optical or electrochemical methods. Test systems of this type are cost-effective and simple to handle. However, a monitored and multistep reaction sequence is not possible using test strips and similar analysis elements. In particular, no control of a chronological sequence of individual reaction steps may be performed.
In contrast, multistep reaction sequences (test protocols) may be performed using wet reagent analytical systems. The high-performance devices allow a multistep reaction sequence, for example, as is necessary in immunochemical analyses. The reaction sequence frequently also comprises the separation of a bound phase and a free phase, a so-called bound/free separation. A plurality of test protocols for determining numerous analytes may be performed using wet reagent analytical systems. Though the test protocols can vary greatly, they all require complex handling with multiple reaction steps. Wet reagent analytical systems usually require technically complex, large-scale devices capable of moving individual elements. The devices used for this purpose are too large, costly, and complex to handle for many applications.
Analytical systems having controllable test elements unify the advantages of both types of analysis systems. They allow externally controlled liquid transport, i.e., a transport that is controlled using an element outside the test element. This external control may be based also on the application of pressure differentials or of change-of-force actions. An external control frequently is performed using centrifugal forces to act on a rotating test element. Nonetheless, these analytical systems are compact and simple to operate.
Controllable test elements typically have a housing comprising a dimensionally-stable plastic material, and at least one analytical-function channel enclosed by the housing. The analytical-function channel often comprises a sequence of multiple channel sections and expanded chambers lying between each section. The structures and dimensions of the analytical-function channel are achieved by profiling of the plastic parts, which are produced by injection-molding technologies or other known methods.
Analytical systems having controllable test elements allow the miniaturization of test protocols that previously required large laboratory systems. Therefore, relatively small quantities of a bodily fluid sample may be analyzed. The relatively small quantities typically are introduced via a dosing station into an analytical-function channel. The analytical-function channel also may be a sample analysis channel. Other analytical-function channels are used, for example, for receiving washing fluid or washing buffers are needed for performing the reaction sequences. Further fluids may be added such as, for example a reaction solution, a washing solution, or a dilution buffer.
Like the bodily fluid sample, also the liquids typically are supplied using a dosing station comprising a dosing pump, such as a piston pump, and a tube for injecting the fluid. The tube may be designated as a dosing needle. In addition, it is also possible to dose the fluids manually, for example, using a manual pipette or a syringe.
To dose small quantities of fluid using a dosing pump, fluid is supplied from a reservoir to a dosing chamber and then is discharged from the dosing chamber by the dosing needle. The volume of the reservoir is many times greater than that of the dosing chamber, so that the quantity of fluid stored in the reservoir is sufficient for a plurality of applications. However, this may also result in problems, because most quantities of fluid are subject to aging and may sit unused for an arbitrarily long time. Some of the fluids needed for the analysis may crystallize after long-term storage. The crystallized fluids then may clog the connection tubing and the dosing pump, requiring complex repairs. To prevent such clogging, the dosing stations must be cleaned and maintained frequently, and the tubing must be replaced regularly.
To avoid contamination, dosing devices known in the prior art comprise a replaceable dosing cartridge, which includes a reservoir, a dosing chamber having dosing piston, and a dosing needle. Systems of this type are known, for example, from US 2005/0035156 A1 and US 2007/0272710 A1.
For many reaction sequences, particularly those involving very small quantities of supplied fluid, the amount of fluid supplied must be very precise. A precision of a few tenths of a microliter is sometimes required. Thus, there remains a continued need for improved methods to precisely dose quantities of fluid being supplied to test elements in wet reagent analytical systems.